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Vascular Function in Chronic Non-communicable Diseases 2.0

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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (31 January 2024) | Viewed by 5674

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Special Issue Editors

Prof. Annalisa Noce

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Guest Editor

UOSD Nephrology and Dialysis, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
Interests: nutrition in chronic kidney disease; haemodialysis; natural active compounds for prevention of non-communicable diseases; body composition assessment; uremic sarcopenia; oxidative stress; microbiome in CKD
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Manfredi Tesauro

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Guest Editor

U.O.C. of Internal Medicine—Center of Hypertension and Nephrology Unit, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
Interests: endothelial dysfunction; obesity; insulin resistance; diabetic nephropathy; metabolic syndrome; adipokines
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Chronic diseases, in particular non-communicable diseases (NCDs) (like diabetes mellitus, cardiovascular diseases, obesity, cancer, and chronic kidney disease) are one of the major causes of mortality and morbidity worldwide. Currently, the number of people affected by chronic NCDs is much higher than in the past. This data is related to the increase in life expectancy and it is especially valid for countries with a high rate of elderly people. Chronic NCDs, in developed countries, weigh heavily on health expenditure. Dysfunction of endothelium and in the vascular system play a pivotal role in the chronic NCDs pathophysiology. This vascular impairment is, in turn, worsened by an increased production of ROS and in an enhanced release of pro-inflammatory cytokines. Oxidative stress and low-grade chronic inflammatory status are peculiar features of chronic NCDs. Therapeutic strategies useful for counteract vascular involvement and the progression of chronic NCDs include moderate exercise, healthy eating habits and the use of drugs exerting an endothelium-protective action. We welcome the submission of original research articles and review articles on signaling mechanisms, novel therapeutic approaches and clinical observations.

Dr. Annalisa Noce
Dr. Manfredi Tesauro
Guest Editors

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Keywords

chronic non-communicable diseases (NCDs)
vascular function
inflammation
atherosclerosis
diabetes
obesity
metabolic syndrome
kidney disease
cancer
reactive oxygen species
novel therapeutic approach

Published Papers (6 papers)

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Research

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13 pages, 3278 KiB

Open AccessArticle

Studying Erythromelalgia Using Doppler Flowmetry Perfusion Signals and Wavelet Analysis—An Exploratory Study

by Luis Monteiro Rodrigues, Joana Caetano, Sergio Faloni Andrade, Clemente Rocha, José Delgado Alves and Hugo Alexandre Ferreira

Biomedicines 2023, 11(12), 3327; https://doi.org/10.3390/biomedicines11123327 - 16 Dec 2023

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Abstract

Erythromelalgia (EM) is a rare disease, which is still poorly characterized. In the present paper, we compared the hand perfusion of one female EM patient, under challenges, with a healthy control group. Using a laser Doppler flowmeter (LDF) with an integrated thermal probe, measurements were taken in both hands at rest (Phase I) and after two separate challenges—post-occlusive hyperemia (PORH) in one arm (A) and reduction of skin temperature (cooling) with ice in one hand (B) (Phase II). The final measurement periods corresponded to recovery (Phases III and IV). The control group involved ten healthy women (27.3 ± 7.9 years old). A second set of measurements was taken in the EM patient one month after beginning a new therapeutic approach with beta-blockers (6.25 mg carvedilol twice daily). Z-scores of the patient’s LDF and temperature fluctuations compared to the control group were assessed using the Wavelet transform (WT) analysis. Here, fluctuations with |Z| > 1.96 were considered significantly different from healthy values, whereas positive or negative Z values indicated higher or lower deviations from the control mean values. Cooling elicited more measurable changes in LDF and temperature fluctuations, especially in higher frequency components (cardiac, respiratory, and myogenic), whereas PORH notably evoked changes in lower frequency components (myogenic, autonomic, and endothelial). No significant Z-score deviations were observed in the second measurement, which might signify a stabilization of the patient’s distal perfusion following the new therapeutic approach. This analysis involving one EM patient, while clearly exploratory, has shown significant deviations in WT-derived physiological components’ values in comparison with the healthy group, confirming the interest in using cold temperature as a challenger. The apparent agreement achieved with the clinical evaluation opens the possibility of expanding this approach to other patients and pathologies in vascular medicine. Full article

(This article belongs to the Special Issue Vascular Function in Chronic Non-communicable Diseases 2.0)

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15 pages, 1771 KiB

Open AccessArticle

Circulating Soluble EPCR Levels Are Reduced in Patients with Ischemic Peripheral Artery Disease and Associated with Markers of Endothelial and Vascular Function

by Janina Krug, Magdalena L. Bochenek, Rajinikanth Gogiraju, Dagmar Laubert-Reh, Karl J. Lackner, Thomas Münzel, Philipp S. Wild, Christine Espinola-Klein and Katrin Schäfer

Biomedicines 2023, 11(9), 2459; https://doi.org/10.3390/biomedicines11092459 - 04 Sep 2023

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Abstract

(1) Background: Endothelial dysfunction initiates cardiovascular pathologies, including peripheral artery disease (PAD). The pathophysiology of impaired new vessel formation in the presence of angiogenic stimuli, such as ischemia and inflammation, is unknown. We have recently shown in mice that reduced endothelial protein C receptor (EPCR) expression results in defective angiogenesis following experimental hindlimb ischemia. (2) Purpose: To determine soluble (s)EPCR levels in the plasma of patients with PAD and to compare them with the protein C activity and biomarkers of endothelial function, inflammation, and angiogenesis. (3) Methods and Results: Clinical tests of vascular function and immunoassays of plasma from patients with PAD stage II were compared to age- and sex-matched individuals with and without cardiovascular risk factors or PAD stage III/IV patients. sEPCR levels were significantly lower in PAD stage II patients compared to subjects with risk factors, but no PAD, and further decreased in PAD stage III/IV patients. Plasma protein C activity or levels of ADAM17, a mediator of EPCR shedding, did not differ. Significant associations between sEPCR and the ankle-brachial index (p = 0.0359), age (p = 0.0488), body mass index (p = 0.0110), and plasma sE-selectin levels (p = 0.0327) were observed. High-sensitive CRP levels and white blood cell counts were significantly elevated in PAD patients and associated with serum glucose levels, but not sEPCR. In contrast, plasma TNFα or IL1β levels did not differ. Circulating levels of VEGF were significantly elevated in PAD stage II patients (p = 0.0198), but not associated with molecular (sE-selectin) or functional (ankle-brachial index) markers of vascular health. (4) Conclusions: Our findings suggest that circulating sEPCR levels may be useful as biomarkers of endothelial dysfunction, including angiogenesis, in persons older than 35 years and that progressive loss of endothelial protein C receptors might be involved in the development and progression of PAD. Full article

(This article belongs to the Special Issue Vascular Function in Chronic Non-communicable Diseases 2.0)

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17 pages, 8198 KiB

Open AccessArticle

Assessment of the Role of Endothelial and Vascular Smooth Muscle EGFR for Acute Blood Pressure Effects of Angiotensin II and Adrenergic Stimulation in Obese Mice

by Barbara Schreier, Christian Stern, Sindy Rabe, Sigrid Mildenberger and Michael Gekle

Biomedicines 2023, 11(8), 2241; https://doi.org/10.3390/biomedicines11082241 - 09 Aug 2023

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Abstract

(1) Background: Obesity is associated with hypertension because of endocrine dysregulation of the adrenergic and the renin–angiotensin–aldosterone systems. The epidermal growth factor receptor (EGFR) is an important signaling hub in the cardiovascular system. In this study, we investigate the role of smooth muscle cell (VSMC) and endothelial cell (EC) EGFRs for blood pressure homeostasis and acute vascular reactivity in vivo. (2) Methods: Mice with deletion of the EGFR in the respective cell type received either a high-fat (HFD) or standard-fat diet (SFD) for 18 weeks. Intravascular blood pressure was measured via a Millar catheter in anesthetized animals upon vehicle load, angiotensin II (AII) and phenylephrine (PE) stimulation. (3) Results: We confirmed that deletion of the EGFR in VSMCs leads to reduced blood pressure and a most probably compensatory heart rate increase. EC-EGFR and VSMC-EGFR had only a minor impact on volume-load-induced blood pressure changes in lean as well as in obese wild-type animals. Regarding vasoactive substances, EC-EGFR seems to have no importance for angiotensin II action and counteracting HFD-induced prolonged blood pressure increase upon PE stimulation. VSMC-EGFR supports the blood pressure response to adrenergic and angiotensin II stimulation in lean animals. The responsiveness to AII and alpha-adrenergic stimulation was similar in lean and obese animals despite the known enhanced activity of the RAAS and the sympathetic nervous system under a high-fat diet. (4) Conclusions: We demonstrate that EGFRs in VSMCs and to a lesser extent in ECs modulate short-term vascular reactivity to AII, catecholamines and volume load in lean and obese animals. Full article

(This article belongs to the Special Issue Vascular Function in Chronic Non-communicable Diseases 2.0)

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12 pages, 1501 KiB

Open AccessArticle

The Association between Serum Adiponectin Levels and Endothelial Function in Non-Dialysis-Dependent Chronic Kidney Disease Patients

by Ming-Chun Chen, Chung-Jen Lee, Yu-Li Lin, Chih-Hsien Wang and Bang-Gee Hsu

Biomedicines 2023, 11(8), 2174; https://doi.org/10.3390/biomedicines11082174 - 02 Aug 2023

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Abstract

Adiponectin is the richest human circulating adipokine with anti-inflammatory, antioxidant, and insulin-sensitizing effects. We evaluated the association between serum adiponectin levels and endothelial function in chronic kidney disease (CKD) patients, obtaining fasting blood samples from 130 non-dialysis CKD subjects. We measured the endothelial function—represented by the vascular reactivity index (VRI)—via non-invasive digital thermal monitoring, and serum adiponectin concentrations by enzyme immunoassay kits. A total of 22 (16.9%), 39 (30.0%), and 69 (53.1%) patients had poor (VRI < 1.0), intermediate (1.0 ≤ VRI < 2.0), and good (VRI ≥ 2.0) vascular reactivity. Elevated serum blood urea nitrogen (BUN) level was negatively correlated with VRI values, but serum adiponectin and estimated glomerular filtration rate were positively associated with VRI values by univariate linear regression analysis. After applying multivariate stepwise linear regression analysis adjustment, the significantly positive association of adiponectin (p < 0.001), and the significantly negative association of log-BUN (p = 0.021) with VRI values in CKD subjects remained. In an animal study using in vitro blood-vessel myography, treatment with adiponectin enhancing acetylcholine-mediated vasorelaxation in 5/6 nephrectomy CKD mice. Our study results indicated that adiponectin concentration was positively associated with VRI values and modulated endothelial function in non-dialysis CKD patients. Full article

(This article belongs to the Special Issue Vascular Function in Chronic Non-communicable Diseases 2.0)

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Review

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16 pages, 2029 KiB

Open AccessReview

Myocardial Ischemia–Reperfusion Injury: Unraveling Pathophysiology, Clinical Manifestations, and Emerging Prevention Strategies

by Marios Sagris, Anastasios Apostolos, Panagiotis Theofilis, Nikolaos Ktenopoulos, Odysseas Katsaros, Sotirios Tsalamandris, Konstantinos Tsioufis, Konstantinos Toutouzas and Dimitris Tousoulis

Biomedicines 2024, 12(4), 802; https://doi.org/10.3390/biomedicines12040802 - 04 Apr 2024

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Abstract

Myocardial ischemia–reperfusion injury (MIRI) remains a challenge in the context of reperfusion procedures for myocardial infarction (MI). While early revascularization stands as the gold standard for mitigating myocardial injury, recent insights have illuminated the paradoxical role of reperfusion, giving rise to the phenomenon known as ischemia–reperfusion injury. This comprehensive review delves into the intricate pathophysiological pathways involved in MIRI, placing a particular focus on the pivotal role of endothelium. Beyond elucidating the molecular intricacies, we explore the diverse clinical manifestations associated with MIRI, underscoring its potential to contribute substantially to the final infarct size, up to 50%. We further navigate through current preventive approaches and highlight promising emerging strategies designed to counteract the devastating effects of the phenomenon. By synthesizing current knowledge and offering a perspective on evolving preventive interventions, this review serves as a valuable resource for clinicians and researchers engaged in the dynamic field of MIRI. Full article

(This article belongs to the Special Issue Vascular Function in Chronic Non-communicable Diseases 2.0)

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16 pages, 1251 KiB

Open AccessReview

The Role of Perivascular Adipose Tissue in the Pathogenesis of Endothelial Dysfunction in Cardiovascular Diseases and Type 2 Diabetes Mellitus

by Alessia Valentini, Carmine Cardillo, David Della Morte and Manfredi Tesauro

Biomedicines 2023, 11(11), 3006; https://doi.org/10.3390/biomedicines11113006 - 09 Nov 2023

Viewed by 1098

Abstract

Cardiovascular diseases (CVDs) and type 2 diabetes mellitus (T2DM) are two of the four major chronic non-communicable diseases (NCDs) representing the leading cause of death worldwide. Several studies demonstrate that endothelial dysfunction (ED) plays a central role in the pathogenesis of these chronic diseases. Although it is well known that systemic chronic inflammation and oxidative stress are primarily involved in the development of ED, recent studies have shown that perivascular adipose tissue (PVAT) is implicated in its pathogenesis, also contributing to the progression of atherosclerosis and to insulin resistance (IR). In this review, we describe the relationship between PVAT and ED, and we also analyse the role of PVAT in the pathogenesis of CVDs and T2DM, further assessing its potential therapeutic target with the aim of restoring normal ED and reducing global cardiovascular risk. Full article

(This article belongs to the Special Issue Vascular Function in Chronic Non-communicable Diseases 2.0)

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